A family of inhibitors of pepsin was isolated from Ascaris lumbricoides var. suum. These proteins which are single bands on polyacrylamide gel electrophoresis inactivate pepsin between pH 2 and pH 5. The interaction of these proteins and procine pepsin are being studied above pH 5 and below pH 2 in order to gain some insight into the mechanism by which inactivation occurs. First, we wish to find out whether a peptide bond in the inhibitor is cleaved when these proteins interact; and second, whether the inhibitor protects the same amino acid residues in pepsin as have been implicated in the catalytic site of pepsin by interpretation of experiments on pepsin using p-bromo-phenacylbromide and N-diazoacetyl-L-phenylalanine methylester plus copper. Chymotrypsin and elastase are inhibited by the same proteins from Ascaris. We are trying to desmonstrate whether the same site or an overlapping site is involved in the reaction between inhibitor and the two proteinases. The primary structure of the component from Ascaris which has been designated chymotrypsin Inhibitor IV is being determined with Dr. D.R. Babin.